ACUTE STROKE AND EARLY MANAGEMENT

Faculty: Jennifer Mandzia MD, PhD, FRCPC Assistant Professor, Western University Co-Medical Director Southwestern Ontario Stroke Network Stroke Neurologist, London Health Sciences Centre Relationships with commercial interests: ► Not applicable Potential for conflict(s) of interest: ► Not applicable

Mitigating Potential Bias ► Not applicable

Objectives • To review the medical management of the acute stroke patient

(ischemic and hemorrhagic stroke) pertaining to antithrombotics, blood pressure control, and investigations

• To review the evidence for acute stroke unit care • To discuss the role and benefit for non-medical interventions in acute

stroke care

STROKE- STATS • Stroke leading cause of adult disability and hospitalization in Canada

(HSF) • Stroke #3 cause of death in Canada (HSF) • Ischemic stroke (IS)

• ~85%

• Hemorrhagic Stroke (ie. Intracranial hemorrhage) (ICH) • ~15% • ICH –high rates of early mortality

Initial ED Evaluation-Hyperacute

• ABCs • Is it a stroke? • Does the patient qualify for acute treatment?

• TIME IS BRAIN

• Standard Blood work (CBC, lytes, renal function INR, aPTT, Troponin, Glucose)

• Standard Brain Imaging including vascular imaging if possible • ECG • Blood Glucose

Goals of early acute stroke management • Manage imminent complications

• i.e. neurological deterioration, ABCs

• Prevent early complications • i.e. UTI, pneumonia, DVT/PE

• Prevent recurrent events and minimize stroke progression • Optimize recovery • Prevent future events

Acute stroke unit care • “A stroke unit is a specialized, geographically defined hospital

unit dedicated to the management of stroke patients and staffed by an experienced inter-professional stroke team”. (CBP 2013)

• Reduces death and disability by up to 30% in patients with mild, moderate and severe stroke (Stroke Unit Trialists collaboration, 2009)

• For all patients with stroke including ICH

What is the evidence for stroke unit care? Cochrane Review: 2013

• Reviewed 28 trials with 5855 patients comparing stroke unit care to standard ward care (21 trials)

• Significant benefit on mortality at 1 year • OR 0.81, 95% CI 0.69 to 0.94; P = 0.005

• Significant effect on reduction of death and dependency • OR 0.79, 95% CI 0.68 to 0.90; P = 0.0007

• No differences based on age, stroke severity, type of stroke, sex • Did not lengthen patient stay

What does an acute stroke unit consist of? • Specialized nursing care and inter-professional team • Implement and follow stroke best practices • Co-location of patients in discrete geographical space

Some time has past: on to the acute stroke care

• Swallowing Assessment (Swallow screen) before food, liquid or pills • Address nutritional needs • Oral care

• Assess for continence: No routine urinary catheters • Assess for fluid status and urinary retention

• Temperature • Monitor and treat > 37.5o C

• Blood glucose • Do not aggressively lower- reasonable to maintain 7.8-10 mmol/L • Treat hypoglycemia

Other core Features of Acute Stroke Unit Care • Functional assessments within 48 h and early mobilization (within 24-48 h)

(AVERT trial 2015) • PT, OT, SLP

• Assess Cognition and depression • Patient and family education • Disposition planning

• Identification of patients who may require palliative care

• Reintegration into the community • Return to work and driving

Case 1

Case 1 • 55 yo M farmer admitted to Bluewater Health with new onset CHF

(EF < 30%), rapid AFIB • PMHX: Left Iliac Occlusion • Meds: Metoprolol, received one dose of Rivaroxaban 20 mg last

night • Social History: current smoker and ETOH~5-8 drinks per day

• Sudden onset right sided weakness and aphasia at 9 am • 130/80, 92 irregular, NIHSS-21 • Blood work- INR 1.7 • CT head done • Telestroke consulted 9:45

1. What is the diagnosis? • Left MCA ischemic stroke- with proximal MCA (M1) occlusion

Back to the Patient • Patient could not receive IV tPA because had received Rivaroxaban the

night before • Transferred to LHSC for thrombectomy • NIHSS-6 at 24 hours

Work-up and management for this patient • Cause of stroke ? i.e. stroke etiology and Risk Factors • Choice of antithrombotic

• ? What is the etiology does that influence your choice in the first 48 hours

• DVT prophylaxis • ?in the setting of hemorrhage

• Functional assessments and Disposition Planning

Stroke Work-up: Etiology • What is the etiology of the stroke?

• Cardioembolic • Large artery disease • Small Vessel Disease • Cryptogenic (ESUS)

• Embolic Strokes Undetermined Source (ESUS)

• Other cause

Assess: A tailored approach to prevent subsequent stroke 1. What are the risk factors? 2. What is etiology or cause? 3. Medication and interventions 4. Non-pharmacologic: Lifestyle changes 5. Continue to monitor for any new events

Basic Investigations Ischemic Stroke (Canadian Stroke Best Practice Guidelines) • Labs

• Fasting lipids, fasting glucose, HbA1C, • Imaging

• Immediate (CT, or MRI if urgently available) [Evidence Level A], and vascular imaging of the brain and neck arteries within 24 hours if not candidate for acute stroke therapy [Level B].

• Cardiac • ECG • Transthoracic Echocardiography-(low yield~ 3% abnormal in TIA patients without heart

disease) [Level B] • Cardiac monitoring: Holter Monitor and consider prolonged monitoring (30 days) in

select cases where AFIB is suspected [Level B] • Other tests: tailored to age group and if no other etiology identified

Acute Antiplatelet Therapy • Acute ASA (within 48 h of onset) reduces risk of early recurrent ischemic

stroke (IS) and long term therapy reduces IS, MI and vascular death (Sandercock et al. 2014); (Rothwell et al. 2016)

• No tPA: not on ASA- 160-325 mg x 1 then 81-325 mg daily- *check

swallowing* • tPA- no antithrombotics for 24 h • Endovascular therapy and no tPA: ? unclear

Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-

course analysis of randomised trials

Prof Peter M Rothwell, FMedSci, Prof Ale Algra, MD, Prof Zhengming Chen, MBBS, Prof Hans-Christoph Diener, MD,

Prof Bo Norrving, PhD, Ziyah Mehta, DPhil

The Lancet Volume 388, Issue 10042, Pages 365-375 (July 2016)

DOI: 10.1016/S0140-6736(16)30468-8

Copyright © 2016 Rothwell et al. Open Access article distributed under the terms of CC BY Terms and Conditions

The Lancet 2016 388, 365-375DOI: (10.1016/S0140-6736(16)30468-8) Copyright © 2016 Rothwell et al. Open Access article distributed under the terms of CC BY Terms and Conditions

Pooled analysis of the early risk of recurrent vascular events in 12 trials of any aspirin versus control

Pooled analysis of the effect of aspirin only versus control in secondary prevention after transient ischaemic attack and ischaemic stroke on the absolute risk of recurrent ischaemic stroke

The Lancet 2016 388, 365-375DOI: (10.1016/S0140-6736(16)30468-8) Copyright © 2016 Rothwell et al. Open Access article distributed under the terms of CC BY Terms and Conditions

Pooled analysis of the effect of aspirin versus control on the severity (mRS score on follow-up) of recurrent IS in the first 6 weeks and the first 12 weeks after randomisation in trials in secondary prevention after TIA and ischaemic stroke

The Lancet 2016 388, 365-375DOI: (10.1016/S0140-6736(16)30468-8) Copyright © 2016 Rothwell et al. Open Access article distributed under the terms of CC BY Terms and Conditions

Choice of Antiplatelets • Choices ASA (81-325 mg), Clopidogrel, Aggrenox, Ticagrelor (Socrates

trial NS) • What Aspirin dose?

• increasing ASA dose increases GI toxic effects • NO evidence for 325 or > mg being superior to 80-81 mg

• Dual antiplatelets: • ASA + Plavix for 3 months started at 24 hours in patients with high risk TIA and

minor stroke is safe and may reduce risk of recurrent stroke at 90 days (Wang et al. CHANCE 2013)

8.2 vs. 11.7 %

Rate of hemorrhagic stroke 0.3% in both groups

What do you do if your patient has a stroke on ASA etc. ?

• Reconsider etiology • Optimize other risk factors • Consider switching to another agent or dual antiplatelets for 21 days in

minor ischemic stroke or TIA if started within 24 hours • Medications reduce risk but do not eliminate risk to 0%

Cochrane Review 2015: acute heparin therapy in ischemic stroke

• Early anticoagulation (within 14 days) in early ischemic stroke (90% within first

48 hours) • 24 trials involving 23,718 participants • Unfractionated Heparin, LMWH, heparinoids, • anticoagulants reduced recurrent stroke (OR 0.76; 95% CI 0.65 to 0.88),

pulmonary embolism(OR 0.60; 95% CI 0.44 to 0.81) , but increased intracranial hemorrhages (OR 2.55; 95% CI 1.95 to 3.33) and extracranial hemorrhage (OR 2.99; 95% CI 2.24 to 3.99).

• Early anticoagulant therapy is not associated with net short- or long-term benefit in people with acute ischaemic stroke or mortality benefit.

• Not recommended routinely in acute ischemic stroke

How about in patients with Atrial Fibrillation?

• Cardioembolic strokes often have hemorrhagic transformation “petechial” • Age of patient and larger lesion size are associated with hemorrhagic

transformation • Lack of evidence to rush in to anticoagulation in patients with ischemic stroke

especially with heparin- within first 48 hours • Risk of early recurrent ischemic stroke is low < 5 % (Berge et al. 2000, IST

1997, TOAST 1998); 0.1-1.3% per day (Paciaroni et al 2016) • Minor stroke likely can start anticoagulation within 3-5 days, TIA earlier after

ICH and large stroke ruled out • Larger strokes 10-14 days (AHA 2014)

Early initiation of anticoagulation with DOACs is it safer and beneficial in patients with non-valvular AFIB ? • Large DOAC trials did not include patients with early stroke or TIA (7-14

days from event) • Seiffge et al. 2016

• SWISS NOACISP registry • 204 patients with AIS/TIA with AFIB started on OAC with VKA or a DOAC • DOAC≤ 7 days vs. DOAC > 7days • 65% DOAC started within 7 days median delay 5 days • 1 ICH in VKA group (4 days after index event) • Recurrent stroke events 6/204, median time-28 days with only 1 patient having

OAC initiated > 7 days

Some scenarios you may anticoagulate earlier • Left ventricular thrombus • Mechanical mitral valve • ?carotid thrombus • Cerebral venous sinus thrombosis

Case 2 • 60 yo F from home • HPI: presented with acute stroke symptoms including aphasia, and mild

right arm weakness • Received IV tPA and endovascular treatment for left M1 occlusion 1h 30

min from symptom onset

• Past Medical History • Right Glomus Tumor • Left leg swelling x 6 months- investigated with u/s negative for DVT • Generally fatigued x several months

• Medications • none

• Social History • Smoker: ½ PPD x 40 years

Course in hospital • Patient develops melena stools and drop in HgB- 95 to 70 • Given history of leg swelling- has u/s bilateral legs- which shows

extensive above the knee bilateral DVT • Transthoracic Echo shows a PFO • Colonoscopy- large rectal mass adenocarcinoma • CT Thorax: hepatic mass and PE

• Diagnosis: L MCA Stroke. Metastatic rectal adenocarcinoma with bilateral DVT and PE

• Etiology ?? • Paradoxical embolization

• ? Treatment of DVT/PE

Venous Thromboembolism prophylaxis and treatment in IS

• ~10% risk of DVT and 1% PE in stroke patients • Risk of major bleeding with heparin DVT prophylaxis in IS

• ~1-2% (EXCLAIM study 2013; Turpie et al.)

• Who is most at risk (CBPR 2016)? • Patients with inability to move one or both lower limbs • Patients who are not independent • Patients who are dehydrated • Patients with cancer

Prevention Options

• Thigh Length Compression Stockings • Alone No benefit (CLOTS1 2009)

• IPC (intermittent Pneumatic Compression Stockings) • ClOTS3 trial(2013): effective at preventing DVT in stroke patients but increased skin

breakdown • Still an option if heparinoids are contra-indicated

• Heparin • Low Molecular Weight Heparin (Enoxparin 40 mg SC) and Unfractionated Heparin in

patients with renal failure • Duration: ?period of immobility; continue if patients are immobile after 30 days (Level

C)

• Early mobilization and hydration

How about ICH patients? • Usually withhold DVT prophylaxis for at least the first 48 hours • Observe for hematoma expansion • Use IPCs • Control BP • Little to no RCT evidence to guide

In this patient • She received an IVC filter placed

Case 3

• 53 yo M acute onset collapse- noted to be aphasic. EMS called • In local ED ? Questionable Seizure • GCS 13, hemiparetic, globally aphasic BP 200/101 • Past medical history: Possible ETOH abuse, HTN, dyslipidemia • Home meds: Irbesartan, Fenofibrate, Nifedipine

Treatment Options 1. Manage conservatively 2. Contact neurosurgery for consultation for hematoma evacuation and

possible external ventricular drain insertion 3. Treat blood pressure with blood pressure target of <160 SBP and < 90

DBP and contact neurosurgery 4. Treat blood pressure with BP target of < 200 SBP and < 110 DBP

Early surgery vs. Initial Conservative treatment (STICH 2) (Mendelow et al. 2013) -307/601 early Surgery (12 hours From symptoms) -Superficial lobar ICH 10-100 ml no IVH -non-comatose pts Results: -no significant diff. in disability at 6 mo. -trend in mortality favouring early surgery group (18 vs. 24% at 6mo)

Acute Blood Pressure Management: ICH • no strong evidence that aggressive blood pressure lowering in ICH

acutely affects long term outcome, including disability or mortality • Evidence suggests that lowering blood pressure to systolic < 140 SBP is

safe acutely, but can be challenging to achieve and resource intensive • Intensive BP lowering may prevent hematoma expansion (Tsivgoulos et

al. 2015)

INTERACT-2 (Anderson et al. 2013) • International multi center RCT • Intensive BP lowering (SBP <140) vs. standard guideline BP lowering

(treat if SBP >180) in patients with ICH within 6 hour of onset • Goal: achieve BP target within 1 hour of randomization • Agent use: not specified; majority used urapidil • Primary Outcome: death or major disability (mRS-3-6) at 90 days

Baseline Characteristics of the Participants.

Primary, Secondary, and Safety Outcomes at 90 Days.

Effect of Early Intensive Blood-Pressure–Lowering Treatment on the Primary Outcome According to Prespecified Subgroups.

Original Article Intensive Blood-Pressure Lowering in Patients

with Acute Cerebral Hemorrhage

Adnan I. Qureshi, M.D., Yuko Y. Palesch, Ph.D., William G. Barsan, M.D., Daniel F. Hanley, M.D., Chung Y. Hsu, M.D., Renee L. Martin, Ph.D., Claudia S. Moy, Ph.D.,

Robert Silbergleit, M.D., Thorsten Steiner, M.D., Jose I. Suarez, M.D., Kazunori Toyoda, M.D., Ph.D., Yongjun Wang, M.D., Haruko Yamamoto, M.D., Ph.D., Byung-

Woo Yoon, M.D., Ph.D., for the ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network

N Engl J Med Volume 375(11):1033-1043

September 15, 2016

Mean Hourly Minimum Systolic Blood Pressure during the First 24 Hours after Randomization, According to Treatment Group.

Qureshi AI et al. N Engl J Med 2016;375:1033-1043

Distribution of Scores on the Modified Rankin Scale, According to Treatment Group.

Qureshi AI et al. N Engl J Med 2016;375:1033-1043

Unadjusted Relative Risk of Death or Disability at 3 Months, According to Subgroup.

Qureshi AI et al. N Engl J Med 2016;375:1033-1043

Primary, Secondary, and Safety Outcomes, According to Treatment Group.

Qureshi AI et al. N Engl J Med 2016;375:1033-1043

MR BP • 65 yo M presents with right sided weakness woke up with symptoms • History of hypertension, diabetes • Meds: Candesartan, amlodipine, crestor, metformin and lantus • BP 190/110 • CT head shows an established left corona radiata stroke

Blood Pressure Management • Treat acutely lower to <140/90 • Admit to hospital treat BP if <220/110, lower by 15% over the next 24

hours, do not exceed 25% • Lower blood pressure to < 185/110 and give tPA

Acute BP lowering in ischemic stroke • BP will lower spontaneously in many in 24-72 hours post stroke • Source of ongoing debate • Also no clear evidence for benefit in improving functional outcome or

reducing mortality in acutely lower BP (CBP 2015) • May be harmful • Avoid precipitous lowering of BP • Consider other acute co-morbidities (i.e. MI, aortic dissection, pregnant)

• Patients eligible for IV tPA: target <185/110 and maintain <180/105 for next 24 hours

• Patients not eligible for IV tPA: treat if SBP >220 or DBP >120 (15% reduction no >25% reduction)

• Reintroduce blood pressure agents slowly if patient on antihypertensive medication after 24-48 hours

Conclusions • Acute stroke care should start right away after the patient has been

stabilized and identified as a stroke/ TIA requiring admission to hospital • Coordinated care teams with expertise in stroke are necessary and

effective in reducing stroke mortality and improving functional outcome from stroke

• Resources and expertise should be concentrated, if possible, in select hospitals to deliver best stroke care